CA1053675A - Isoquinoline derivatives and process for the production thereof - Google Patents

Isoquinoline derivatives and process for the production thereof

Info

Publication number: CA1053675A
Authority: CA; Canada
Prior art keywords: compound; formula; acid; methyl; carbon atoms
Prior art date: 1973-12-10
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.): Expired

Application number

CA215,386A

Other languages

English (en)

French (fr)

Other versions

CA215386S (en

Inventor

Werner Mehrhof

Karl H. Becker

Rolf Pohlke

Hans-Jochen Schliep

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Merck Patent GmbH

Original Assignee

Merck Patent GmbH

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1973-12-10

Filing date

1974-12-06

Publication date

1979-05-01

1974-12-06 Application filed by Merck Patent GmbH filed Critical Merck Patent GmbH

1979-05-01 Application granted granted Critical

1979-05-01 Publication of CA1053675A publication Critical patent/CA1053675A/en

Status Expired legal-status Critical Current

Links

238000000034 method Methods 0.000 title claims description 32
238000004519 manufacturing process Methods 0.000 title claims description 3
125000002183 isoquinolinyl group Chemical class C1(=NC=CC2=CC=CC=C12)* 0.000 title abstract description 3
-1 methoxybenzoyl Chemical group 0.000 claims abstract description 65
239000002253 acid Substances 0.000 claims abstract description 32
125000000217 alkyl group Chemical group 0.000 claims abstract description 28
125000004432 carbon atom Chemical group C* 0.000 claims abstract description 22
150000003839 salts Chemical class 0.000 claims abstract description 21
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 12
SJSOFNCYXJUNBT-UHFFFAOYSA-N 3,4,5-trimethoxybenzoic acid Chemical compound COC1=CC(C(O)=O)=CC(OC)=C1OC SJSOFNCYXJUNBT-UHFFFAOYSA-N 0.000 claims abstract description 8
125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims abstract description 8
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims abstract description 8
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims abstract description 8
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 7
150000003242 quaternary ammonium salts Chemical class 0.000 claims abstract description 7
125000001589 carboacyl group Chemical group 0.000 claims abstract description 6
125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims abstract description 6
125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims abstract description 5
IWPZKOJSYQZABD-UHFFFAOYSA-N 3,4,5-trimethoxybenzoic acid Natural products COC1=CC(OC)=CC(C(O)=O)=C1 IWPZKOJSYQZABD-UHFFFAOYSA-N 0.000 claims abstract description 4
125000005809 3,4,5-trimethoxyphenyl group Chemical group [H]C1=C(OC([H])([H])[H])C(OC([H])([H])[H])=C(OC([H])([H])[H])C([H])=C1* 0.000 claims abstract description 4
150000001875 compounds Chemical class 0.000 claims description 42
239000003795 chemical substances by application Substances 0.000 claims description 28
230000000875 corresponding effect Effects 0.000 claims description 25
238000011282 treatment Methods 0.000 claims description 19
239000000047 product Substances 0.000 claims description 14
AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 claims description 12
150000002537 isoquinolines Chemical class 0.000 claims description 12
239000003054 catalyst Substances 0.000 claims description 11
239000000126 substance Substances 0.000 claims description 10
UWYZHKAOTLEWKK-UHFFFAOYSA-N 1,2,3,4-tetrahydroisoquinoline Chemical class C1=CC=C2CNCCC2=C1 UWYZHKAOTLEWKK-UHFFFAOYSA-N 0.000 claims description 7
239000003638 chemical reducing agent Substances 0.000 claims description 7
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 7
YRERIFLPJACTLF-UHFFFAOYSA-N 3,4,5-trimethoxy-n-[(3-methyl-1,2,3,4-tetrahydroisoquinolin-1-yl)methyl]benzamide Chemical group COC1=C(OC)C(OC)=CC(C(=O)NCC2C3=CC=CC=C3CC(C)N2)=C1 YRERIFLPJACTLF-UHFFFAOYSA-N 0.000 claims description 6
239000007795 chemical reaction product Substances 0.000 claims description 6
VPHHEAKNEVIBEP-UHFFFAOYSA-N 3,4,5-trimethoxy-n-(2-oxoethyl)benzamide Chemical compound COC1=CC(C(=O)NCC=O)=CC(OC)=C1OC VPHHEAKNEVIBEP-UHFFFAOYSA-N 0.000 claims description 4
DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 claims description 4
FVVJVTSODPWHBU-UHFFFAOYSA-N n-(cyanomethyl)-3,4,5-trimethoxybenzamide Chemical compound COC1=CC(C(=O)NCC#N)=CC(OC)=C1OC FVVJVTSODPWHBU-UHFFFAOYSA-N 0.000 claims description 4
125000002777 acetyl group Chemical class [H]C([H])([H])C(*)=O 0.000 claims description 3
150000008065 acid anhydrides Chemical class 0.000 claims description 3
229910052717 sulfur Inorganic materials 0.000 claims description 3
CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 claims description 2
150000008064 anhydrides Chemical class 0.000 claims description 2
150000001540 azides Chemical class 0.000 claims description 2
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 2
125000005843 halogen group Chemical group 0.000 claims description 2
229910052760 oxygen Inorganic materials 0.000 claims description 2
NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 claims 2
239000012458 free base Substances 0.000 claims 1
125000002924 primary amino group Chemical class [H]N([H])* 0.000 abstract description 4
230000005792 cardiovascular activity Effects 0.000 abstract 1
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 42
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 36
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 24
239000000243 solution Substances 0.000 description 23
239000000203 mixture Substances 0.000 description 19
229960001701 chloroform Drugs 0.000 description 18
238000006243 chemical reaction Methods 0.000 description 15
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 14
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 12
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 12
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 10
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 10
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 8
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 8
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 8
150000007513 acids Chemical class 0.000 description 7
239000002585 base Substances 0.000 description 7
BUHYMJLFRZAFBF-UHFFFAOYSA-N 3,4,5-trimethoxybenzoyl chloride Chemical compound COC1=CC(C(Cl)=O)=CC(OC)=C1OC BUHYMJLFRZAFBF-UHFFFAOYSA-N 0.000 description 6
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 6
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
230000010933 acylation Effects 0.000 description 6
238000005917 acylation reaction Methods 0.000 description 6
150000001412 amines Chemical class 0.000 description 6
238000001704 evaporation Methods 0.000 description 6
230000008020 evaporation Effects 0.000 description 6
BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Substances [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 6
239000002904 solvent Substances 0.000 description 6
239000007858 starting material Substances 0.000 description 6
239000003826 tablet Substances 0.000 description 6
OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 5
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 5
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
235000019253 formic acid Nutrition 0.000 description 5
238000005984 hydrogenation reaction Methods 0.000 description 5
239000012442 inert solvent Substances 0.000 description 5
229910000510 noble metal Inorganic materials 0.000 description 5
238000007363 ring formation reaction Methods 0.000 description 5
150000003526 tetrahydroisoquinolines Chemical class 0.000 description 5
150000001805 chlorine compounds Chemical class 0.000 description 4
235000011167 hydrochloric acid Nutrition 0.000 description 4
229960000443 hydrochloric acid Drugs 0.000 description 4
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
229910000028 potassium bicarbonate Inorganic materials 0.000 description 4
239000000741 silica gel Substances 0.000 description 4
229910002027 silica gel Inorganic materials 0.000 description 4
BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 3
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 3
OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 3
229910019020 PtO2 Inorganic materials 0.000 description 3
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 3
YKIOKAURTKXMSB-UHFFFAOYSA-N adams's catalyst Chemical compound O=[Pt]=O YKIOKAURTKXMSB-UHFFFAOYSA-N 0.000 description 3
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
229910017052 cobalt Inorganic materials 0.000 description 3
239000010941 cobalt Substances 0.000 description 3
GUTLYIVDDKVIGB-UHFFFAOYSA-N cobalt atom Chemical compound [Co] GUTLYIVDDKVIGB-UHFFFAOYSA-N 0.000 description 3
239000008298 dragée Substances 0.000 description 3
238000001035 drying Methods 0.000 description 3
238000007327 hydrogenolysis reaction Methods 0.000 description 3
INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 3
229910052759 nickel Inorganic materials 0.000 description 3
229910052697 platinum Inorganic materials 0.000 description 3
239000011591 potassium Substances 0.000 description 3
229910052700 potassium Inorganic materials 0.000 description 3
235000015497 potassium bicarbonate Nutrition 0.000 description 3
239000011736 potassium bicarbonate Substances 0.000 description 3
TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 3
239000000454 talc Substances 0.000 description 3
229910052623 talc Inorganic materials 0.000 description 3
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
GAIKGQYGTJKHRA-UHFFFAOYSA-N (3-methyl-1,2,3,4-tetrahydroisoquinolin-1-yl)methanamine Chemical compound C1=CC=C2C(CN)NC(C)CC2=C1 GAIKGQYGTJKHRA-UHFFFAOYSA-N 0.000 description 2
SPEUIVXLLWOEMJ-UHFFFAOYSA-N 1,1-dimethoxyethane Chemical compound COC(C)OC SPEUIVXLLWOEMJ-UHFFFAOYSA-N 0.000 description 2
RFFLAFLAYFXFSW-UHFFFAOYSA-N 1,2-dichlorobenzene Chemical compound ClC1=CC=CC=C1Cl RFFLAFLAYFXFSW-UHFFFAOYSA-N 0.000 description 2
IOEPOEDBBPRAEI-UHFFFAOYSA-N 1,2-dihydroisoquinoline Chemical class C1=CC=C2CNC=CC2=C1 IOEPOEDBBPRAEI-UHFFFAOYSA-N 0.000 description 2
MPPPKRYCTPRNTB-UHFFFAOYSA-N 1-bromobutane Chemical compound CCCCBr MPPPKRYCTPRNTB-UHFFFAOYSA-N 0.000 description 2
PXXARNZMKJIEDO-UHFFFAOYSA-N 3,4,5-trimethoxy-n-(1,2,3,4-tetrahydroisoquinolin-1-ylmethyl)benzamide Chemical compound COC1=C(OC)C(OC)=CC(C(=O)NCC2C3=CC=CC=C3CCN2)=C1 PXXARNZMKJIEDO-UHFFFAOYSA-N 0.000 description 2
ABFKVMMWXAKIPB-UHFFFAOYSA-N 3,4,5-trimethoxy-n-[(3-methylisoquinolin-1-yl)methyl]benzamide Chemical compound COC1=C(OC)C(OC)=CC(C(=O)NCC=2C3=CC=CC=C3C=C(C)N=2)=C1 ABFKVMMWXAKIPB-UHFFFAOYSA-N 0.000 description 2
NKSZCPBUWGZONP-UHFFFAOYSA-N 3,4-dihydroisoquinoline Chemical class C1=CC=C2C=NCCC2=C1 NKSZCPBUWGZONP-UHFFFAOYSA-N 0.000 description 2
ANOUKFYBOAKOIR-UHFFFAOYSA-N 3,4-dimethoxyphenylethylamine Chemical compound COC1=CC=C(CCN)C=C1OC ANOUKFYBOAKOIR-UHFFFAOYSA-N 0.000 description 2
FVVXWRGARUACNW-UHFFFAOYSA-N 3-methylisoquinoline Chemical compound C1=CC=C2C=NC(C)=CC2=C1 FVVXWRGARUACNW-UHFFFAOYSA-N 0.000 description 2
CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
241000282472 Canis lupus familiaris Species 0.000 description 2
BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 2
RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 2
ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 2
VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
JVTAAEKCZFNVCJ-REOHCLBHSA-N L-lactic acid Chemical compound C[C@H](O)C(O)=O JVTAAEKCZFNVCJ-REOHCLBHSA-N 0.000 description 2
GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
239000002841 Lewis acid Substances 0.000 description 2
YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
208000002193 Pain Diseases 0.000 description 2
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 2
239000007868 Raney catalyst Substances 0.000 description 2
229910000564 Raney nickel Inorganic materials 0.000 description 2
229910008046 SnC14 Inorganic materials 0.000 description 2
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 2
235000011054 acetic acid Nutrition 0.000 description 2
230000002378 acidificating effect Effects 0.000 description 2
230000029936 alkylation Effects 0.000 description 2
238000005804 alkylation reaction Methods 0.000 description 2
BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 2
125000003277 amino group Chemical group 0.000 description 2
125000003118 aryl group Chemical group 0.000 description 2
HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 2
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
239000000872 buffer Substances 0.000 description 2
238000009903 catalytic hydrogenation reaction Methods 0.000 description 2
MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 2
HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
238000004587 chromatography analysis Methods 0.000 description 2
XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
230000000694 effects Effects 0.000 description 2
150000002148 esters Chemical class 0.000 description 2
239000000706 filtrate Substances 0.000 description 2
230000002140 halogenating effect Effects 0.000 description 2
125000000623 heterocyclic group Chemical group 0.000 description 2
229910052739 hydrogen Inorganic materials 0.000 description 2
239000001257 hydrogen Substances 0.000 description 2
125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
150000004694 iodide salts Chemical class 0.000 description 2
SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 2
TWBYWOBDOCUKOW-UHFFFAOYSA-N isonicotinic acid Chemical compound OC(=O)C1=CC=NC=C1 TWBYWOBDOCUKOW-UHFFFAOYSA-N 0.000 description 2
JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
239000008101 lactose Substances 0.000 description 2
150000007517 lewis acids Chemical class 0.000 description 2
239000007788 liquid Substances 0.000 description 2
235000019359 magnesium stearate Nutrition 0.000 description 2
235000011090 malic acid Nutrition 0.000 description 2
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YYKUMMPSKNYMLV-UHFFFAOYSA-N n-[(3-ethyl-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinolin-1-yl)methyl]-3,4,5-trimethoxybenzamide Chemical compound N1C(CC)CC2=CC(OC)=C(OC)C=C2C1CNC(=O)C1=CC(OC)=C(OC)C(OC)=C1 YYKUMMPSKNYMLV-UHFFFAOYSA-N 0.000 description 1
BJCLKHCOOFCQFQ-UHFFFAOYSA-N n-[(3-ethyl-6,7-dimethoxyisoquinolin-1-yl)methyl]-3,4,5-trimethoxybenzamide Chemical compound N=1C(CC)=CC2=CC(OC)=C(OC)C=C2C=1CNC(=O)C1=CC(OC)=C(OC)C(OC)=C1 BJCLKHCOOFCQFQ-UHFFFAOYSA-N 0.000 description 1
FLECVDMCRRWAJF-UHFFFAOYSA-N n-[(3-ethylisoquinolin-1-yl)methyl]-3,4,5-trimethoxybenzamide Chemical compound N=1C(CC)=CC2=CC=CC=C2C=1CNC(=O)C1=CC(OC)=C(OC)C(OC)=C1 FLECVDMCRRWAJF-UHFFFAOYSA-N 0.000 description 1
RKFICTMIVJKSJS-UHFFFAOYSA-N n-[(6,7-dimethoxy-1,2,3,4-tetrahydroisoquinolin-1-yl)methyl]-3,4,5-trimethoxybenzamide Chemical compound C1=2C=C(OC)C(OC)=CC=2CCNC1CNC(=O)C1=CC(OC)=C(OC)C(OC)=C1 RKFICTMIVJKSJS-UHFFFAOYSA-N 0.000 description 1
AESFFQGKDOITBB-UHFFFAOYSA-N n-[(6,7-dimethoxy-3,4-dihydroisoquinolin-1-yl)methyl]-3,4,5-trimethoxybenzamide Chemical compound C1=2C=C(OC)C(OC)=CC=2CCN=C1CNC(=O)C1=CC(OC)=C(OC)C(OC)=C1 AESFFQGKDOITBB-UHFFFAOYSA-N 0.000 description 1
CBWKSOOYLQVIMU-UHFFFAOYSA-N n-[(6,7-dimethoxy-3-methyl-1,2,3,4-tetrahydroisoquinolin-1-yl)methyl]-3,4,5-trimethoxybenzamide Chemical compound C1=2C=C(OC)C(OC)=CC=2CC(C)NC1CNC(=O)C1=CC(OC)=C(OC)C(OC)=C1 CBWKSOOYLQVIMU-UHFFFAOYSA-N 0.000 description 1
IWIWSXCKRWGQCA-UHFFFAOYSA-N n-[(6,7-dimethoxyisoquinolin-1-yl)methyl]-3,4,5-trimethoxybenzamide Chemical compound COC1=C(OC)C(OC)=CC(C(=O)NCC=2C3=CC(OC)=C(OC)C=C3C=CN=2)=C1 IWIWSXCKRWGQCA-UHFFFAOYSA-N 0.000 description 1
GDWBJEGDXAZCBU-UHFFFAOYSA-N n-[[2-(2-chloroethyl)-3,4-dihydro-1h-isoquinolin-1-yl]methyl]benzamide Chemical compound ClCCN1CCC2=CC=CC=C2C1CNC(=O)C1=CC=CC=C1 GDWBJEGDXAZCBU-UHFFFAOYSA-N 0.000 description 1
QZWCSXIPMDJNHC-UHFFFAOYSA-N n-[[2-(2-hydroxy-3-morpholin-4-ylpropyl)-3,4-dihydro-1h-isoquinolin-1-yl]methyl]benzamide Chemical compound C1CC2=CC=CC=C2C(CNC(=O)C=2C=CC=CC=2)N1CC(O)CN1CCOCC1 QZWCSXIPMDJNHC-UHFFFAOYSA-N 0.000 description 1
125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
229910017604 nitric acid Inorganic materials 0.000 description 1
150000002825 nitriles Chemical class 0.000 description 1
125000004971 nitroalkyl group Chemical group 0.000 description 1
125000004433 nitrogen atom Chemical group N* 0.000 description 1
LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 description 1
125000001402 nonanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
125000002801 octanoyl group Chemical group C(CCCCCCC)(=O)* 0.000 description 1
239000003921 oil Substances 0.000 description 1
235000019198 oils Nutrition 0.000 description 1
239000002674 ointment Substances 0.000 description 1
230000003287 optical effect Effects 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
235000005985 organic acids Nutrition 0.000 description 1
239000011368 organic material Substances 0.000 description 1
239000003960 organic solvent Substances 0.000 description 1
230000003204 osmotic effect Effects 0.000 description 1
235000006408 oxalic acid Nutrition 0.000 description 1
150000002923 oximes Chemical class 0.000 description 1
229910052763 palladium Inorganic materials 0.000 description 1
FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 1
239000000546 pharmaceutical excipient Substances 0.000 description 1
239000000825 pharmaceutical preparation Substances 0.000 description 1
230000000144 pharmacologic effect Effects 0.000 description 1
150000007925 phenylethylamine derivatives Chemical class 0.000 description 1
150000003016 phosphoric acids Chemical class 0.000 description 1
UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 1
IPNPIHIZVLFAFP-UHFFFAOYSA-N phosphorus tribromide Chemical compound BrP(Br)Br IPNPIHIZVLFAFP-UHFFFAOYSA-N 0.000 description 1
IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 description 1
229920001223 polyethylene glycol Polymers 0.000 description 1
229910000027 potassium carbonate Inorganic materials 0.000 description 1
235000011181 potassium carbonates Nutrition 0.000 description 1
239000000843 powder Substances 0.000 description 1
239000003755 preservative agent Substances 0.000 description 1
235000019260 propionic acid Nutrition 0.000 description 1
125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical group CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 description 1
239000008262 pumice Substances 0.000 description 1
238000000746 purification Methods 0.000 description 1
IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
239000000376 reactant Substances 0.000 description 1
229960004889 salicylic acid Drugs 0.000 description 1
229910052711 selenium Inorganic materials 0.000 description 1
239000011669 selenium Substances 0.000 description 1
235000017557 sodium bicarbonate Nutrition 0.000 description 1
229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
239000012279 sodium borohydride Substances 0.000 description 1
229910000033 sodium borohydride Inorganic materials 0.000 description 1
235000017550 sodium carbonate Nutrition 0.000 description 1
MNWBNISUBARLIT-UHFFFAOYSA-N sodium cyanide Chemical compound [Na+].N#[C-] MNWBNISUBARLIT-UHFFFAOYSA-N 0.000 description 1
239000007787 solid Substances 0.000 description 1
239000011877 solvent mixture Substances 0.000 description 1
238000003797 solvolysis reaction Methods 0.000 description 1
239000003381 stabilizer Substances 0.000 description 1
239000008107 starch Substances 0.000 description 1
235000019698 starch Nutrition 0.000 description 1
229910000018 strontium carbonate Inorganic materials 0.000 description 1
125000001424 substituent group Chemical group 0.000 description 1
238000006467 substitution reaction Methods 0.000 description 1
150000003460 sulfonic acids Chemical class 0.000 description 1
239000011593 sulfur Substances 0.000 description 1
239000000829 suppository Substances 0.000 description 1
230000001629 suppression Effects 0.000 description 1
239000000725 suspension Substances 0.000 description 1
239000006188 syrup Substances 0.000 description 1
235000020357 syrup Nutrition 0.000 description 1
235000012222 talc Nutrition 0.000 description 1
UGNWTBMOAKPKBL-UHFFFAOYSA-N tetrachloro-1,4-benzoquinone Chemical compound ClC1=C(Cl)C(=O)C(Cl)=C(Cl)C1=O UGNWTBMOAKPKBL-UHFFFAOYSA-N 0.000 description 1
HPGGPRDJHPYFRM-UHFFFAOYSA-J tin(iv) chloride Chemical compound Cl[Sn](Cl)(Cl)Cl HPGGPRDJHPYFRM-UHFFFAOYSA-J 0.000 description 1
239000000196 tragacanth Substances 0.000 description 1
235000010487 tragacanth Nutrition 0.000 description 1
229940116362 tragacanth Drugs 0.000 description 1
125000005270 trialkylamine group Chemical group 0.000 description 1
RKBCYCFRFCNLTO-UHFFFAOYSA-N triisopropylamine Chemical compound CC(C)N(C(C)C)C(C)C RKBCYCFRFCNLTO-UHFFFAOYSA-N 0.000 description 1
125000003774 valeryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
229940099259 vaseline Drugs 0.000 description 1
235000015112 vegetable and seed oil Nutrition 0.000 description 1
239000008158 vegetable oil Substances 0.000 description 1
239000000080 wetting agent Substances 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
- C07D217/22—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the nitrogen-containing ring
- C07D217/26—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
- C07D217/12—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with radicals, substituted by hetero atoms, attached to carbon atoms of the nitrogen-containing ring
- C07D217/14—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with radicals, substituted by hetero atoms, attached to carbon atoms of the nitrogen-containing ring other than aralkyl radicals

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Other In-Based Heterocyclic Compounds (AREA)

CA215,386A 1973-12-10 1974-12-06 Isoquinoline derivatives and process for the production thereof Expired CA1053675A (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
DE2361390A DE2361390A1 (de)	1973-12-10	1973-12-10	Isochinolinderivate und verfahren zu ihrer herstellung

Publications (1)

Publication Number	Publication Date
CA1053675A true CA1053675A (en)	1979-05-01

Family

ID=5900348

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA215,386A Expired CA1053675A (en)	1973-12-10	1974-12-06	Isoquinoline derivatives and process for the production thereof

Country Status (18)

Country	Link
US (1)	US3985881A (da)
JP (1)	JPS5088077A (da)
AT (1)	AT351026B (da)
BE (1)	BE823027A (da)
CA (1)	CA1053675A (da)
CH (1)	CH605776A5 (da)
CS (1)	CS188933B2 (da)
DD (1)	DD115666A5 (da)
DE (1)	DE2361390A1 (da)
DK (1)	DK137007C (da)
ES (1)	ES432716A1 (da)
FR (1)	FR2253522B1 (da)
GB (1)	GB1447611A (da)
HU (1)	HU171483B (da)
IL (1)	IL46160A0 (da)
NL (1)	NL7416050A (da)
SE (1)	SE7415247L (da)
ZA (1)	ZA747820B (da)

Families Citing this family (20)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
DE2504250A1 (de) *	1975-02-01	1976-08-05	Merck Patent Gmbh	Tetrahydroisochinolin-derivate und verfahren zu ihrer herstellung
US4232160A (en) *	1978-10-18	1980-11-04	Miles Laboratories, Inc.	Isoquinoline propionamides exhibiting analgesic properties
US4556712A (en) *	1981-05-20	1985-12-03	The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services	Preparation and racemization of chiral 1-benzyl-1,2,3,4-tetrahydroisoquinolines
GB8601796D0 (en) *	1986-01-24	1986-02-26	Zambeletti Spa L	Compounds
DE3713743A1 (de) *	1987-04-24	1988-11-17	Boehringer Ingelheim Kg	Kondensierte bis-(3,4-dihydro-l-pyridinyl)methane, verfahren zu ihrer herstellung und diese verbindungen enthaltende arzneimittel
ES2061972T3 (es) *	1988-02-19	1994-12-16	Smithkline Beecham Farma	1,2,3,4-tetrahidroisoquinoleinas, procedimiento para su preparacion y su uso como agonistas kapa-receptores.
PT89780A (pt) *	1988-02-23	1989-10-04	Glaxo Group Ltd	Processo para a preparacao de derivados da tetrahidroisoquinolina
DE3827727A1 (de) *	1988-08-16	1990-02-22	Boehringer Ingelheim Kg	Anellierte tetrahydropyridinessigsaeurederivate, verfahren zu deren herstellung und verwendung solcher verbindungen zur kardioprotektion
GB8827479D0 (en) *	1988-11-24	1988-12-29	Zambeletti Spa L	Novel compounds
GB8916395D0 (en) *	1989-07-18	1989-09-06	Zambeletti Spa L	Pharmaceuticals
US5389638A (en) *	1993-09-10	1995-02-14	Abbott Laboratories	Tetrahydroisoquinolines as alpha-2 antagonists and biogenic amine uptake inhibitors
GB0225884D0 (en) *	2002-11-06	2002-12-11	Glaxo Group Ltd	Novel compounds
US8993555B2 (en) *	2012-12-21	2015-03-31	Epizyme, Inc.	PRMT5 inhibitors and uses thereof
CA2996813C (en) *	2015-09-01	2023-09-26	Merck Patent Gmbh	Method for the production of praziquantel and precursors thereof
US20180305334A1 (en) *	2015-10-14	2018-10-25	Aquinnah Pharmaceuticals, Inc.	Compounds, compositions and methods of use against stress granules
SG11202002032SA (en)	2017-09-22	2020-04-29	Jubilant Epipad LLC	Heterocyclic compounds as pad inhibitors
CA3076476A1 (en)	2017-10-18	2019-04-25	Jubilant Epipad LLC	Imidazo-pyridine compounds as pad inhibitors
BR112020008851A2 (pt)	2017-11-06	2020-10-20	Jubilant Prodel LLC	composto da fórmula i, processo de preparação de compostos da fórmula i, composição farmacêutica, método para o tratamento e/ou prevenção de várias doenças, uso, método para o tratamento de câncer, método de tratamento de câncer e método para o tratamento e/ou prevenção de câncer e doenças infecciosas
PL3704120T3 (pl)	2017-11-24	2024-09-16	Jubilant Episcribe Llc	Związki heterocykliczne jako inhibitory prmt5
SG11202008950PA (en)	2018-03-13	2020-10-29	Jubilant Prodel LLC	Bicyclic compounds as inhibitors of pd1/pd-l1 interaction/activation

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US2612503A (en) *	1949-04-19	1952-09-30	Smith Kline French Lab	Basic ether-substituted isoquinolines
US2640829A (en) *	1950-11-10	1953-06-02	Smith Kline French Lab	Isoquinolyl heterocyclic ethers
US3021331A (en) *	1959-07-20	1962-02-13	Pfizer & Co C	Azabenzopyridocolines
US3483206A (en) *	1967-12-15	1969-12-09	Ciba Geigy Corp	N-isoquinolylalkanoyl-n-arylamines
US3600394A (en) *	1968-05-17	1971-08-17	Searle & Co	2-aminoalkyl-3-arylisocarbostyrils

1973
- 1973-12-10 DE DE2361390A patent/DE2361390A1/de active Pending
1974
- 1974-11-29 IL IL46160A patent/IL46160A0/xx unknown
- 1974-12-05 SE SE7415247A patent/SE7415247L/xx unknown
- 1974-12-06 BE BE151221A patent/BE823027A/xx unknown
- 1974-12-06 CS CS748365A patent/CS188933B2/cs unknown
- 1974-12-06 CA CA215,386A patent/CA1053675A/en not_active Expired
- 1974-12-06 FR FR7440041A patent/FR2253522B1/fr not_active Expired
- 1974-12-09 GB GB5319174A patent/GB1447611A/en not_active Expired
- 1974-12-09 JP JP49141945A patent/JPS5088077A/ja active Pending
- 1974-12-09 ZA ZA00747820A patent/ZA747820B/xx unknown
- 1974-12-09 HU HU74ME00001812A patent/HU171483B/hu unknown
- 1974-12-09 CH CH1632774A patent/CH605776A5/xx not_active IP Right Cessation
- 1974-12-09 DK DK639674A patent/DK137007C/da active
- 1974-12-09 AT AT981974A patent/AT351026B/de not_active IP Right Cessation
- 1974-12-09 US US05/530,551 patent/US3985881A/en not_active Expired - Lifetime
- 1974-12-09 ES ES432716A patent/ES432716A1/es not_active Expired
- 1974-12-09 DD DD182514A patent/DD115666A5/xx unknown
- 1974-12-10 NL NL7416050A patent/NL7416050A/xx not_active Application Discontinuation

Also Published As

Publication number	Publication date
SE7415247L (da)	1975-06-11
DE2361390A1 (de)	1975-06-19
ZA747820B (en)	1975-12-31
ATA981974A (de)	1978-12-15
DD115666A5 (da)	1975-10-12
ES432716A1 (es)	1977-03-01
FR2253522A1 (da)	1975-07-04
GB1447611A (en)	1976-08-25
CH605776A5 (da)	1978-10-13
FR2253522B1 (da)	1978-06-30
PL93405B1 (da)	1977-05-30
DK639674A (da)	1975-08-11
AU7625774A (en)	1976-06-10
HU171483B (hu)	1978-01-28
US3985881A (en)	1976-10-12
DK137007C (da)	1978-06-05
CS188933B2 (en)	1979-03-30
NL7416050A (nl)	1975-06-12
BE823027A (fr)	1975-06-06
AT351026B (de)	1979-07-10
DK137007B (da)	1978-01-02
IL46160A0 (en)	1975-02-10
JPS5088077A (da)	1975-07-15

Publication	Publication Date	Title
US3985881A (en)	1976-10-12	1(3,4,5-Trimethoxybenzamido methyl) tetrahydro isoquinoline derivatives and a process for their production
US3631055A (en)	1971-12-28	Thiazolyl and pyridyl aminoalcohols
US3950343A (en)	1976-04-13	Pyrroloisoquinoline derivatives
AU621071B2 (en)	1992-03-05	1,7-annelated indolecarboxylic acid esters and amides
US3272707A (en)	1966-09-13	Pharmaceutical compositions and methods for their use
NZ230068A (en)	1991-07-26	Indazole-3-carboxylic acid esters and amides of diaza compounds having 6,7, or 8 ring members: preparatory processes and pharmaceutical compositions
US3714149A (en)	1973-01-30	Pyridobenzodiazepinones
AU682768B2 (en)	1997-10-16	Bicyclic amidine derivatives as inhibitors of nitric oxide synthetase
CA2006413A1 (en)	1990-06-23	Nitrogen-containing ring compounds
US3557119A (en)	1971-01-19	2,3,7,8,9,9a-hexahydro-1h-benzo(d,e)(1,7) naphthyridine derivatives
JPH01100167A (ja)	1989-04-18	２−［（４−ピペリジル）メチル］−１，２，３，４−テトラヒドロイソキノリン誘導体
US3823148A (en)	1974-07-09	4-biphenylyl isoquinoline derivatives
AU701329B2 (en)	1999-01-28	Amidine and isothiourea derivatives as inhibitors of nitric oxide synthase
US3793329A (en)	1974-02-19	N-(furyl-methyl)-3-oxy-morphinans and salts thereof
US3131191A (en)	1964-04-28	Process for the preparation of noraporphines
Craig et al.	1948	Curariform Activity and Chemical Structure. II. Synthesis in the Benzyltetrahydroisoquinoline Series1
SK16896A3 (en)	1996-10-02	1-£2-(substituted vinyl)\|-3,4-dihydro-5h-2,3-benzodiazepine derivatives
AU640259B2 (en)	1993-08-19	Process for the preparation of 1-alkylisoquinoline derivatives
CA2137611A1 (en)	1995-06-10	Epi-epibatidine derivatives
US3557122A (en)	1971-01-19	5,6,7a,8,11,11a,12,12a-octahydroindolo (2,1-a)isoquinolin-9(10h)-ones
US3415831A (en)	1968-12-10	2-isoquinolinyl(and carbolinyl) alkyloctahydroindolo [2,3-a]-quinolizines
US5198437A (en)	1993-03-30	1,7-annelated indolecarboxylic acid esters and amides
US3133926A (en)	1964-05-19	1-(pyridyl-lower alkyl)-1, 2, 3, 4-tetrahydro-isoquinolines
US3067203A (en)	1962-12-04	Tetrahybroisqquinoline derivatives
Gootjes et al.	1965	Derivatives of benzo‐and indolo‐quinolizines: I Synthesis of 2‐substituted hexahydro‐2H‐benzo [a] quinolizines and octahydroindolo [2, 3‐a] quinolizines from substituted glutaric acids